Low- and no-calorie sweeteners (LNCS) are food additives that have been widely consumed for many decades. Their safety has been well established by authoritative bodies globally and is re-evaluated periodically. The objective herein was to survey and summarize the genotoxicity potential of five commonly utilized LNCS: acesulfame potassium (Ace-K), aspartame, saccharin, steviol glycosides and sucralose. Data from peer-reviewed literature and the ToxCast/Tox21 database were evaluated and integrated with the most recent weight-of-evidence evaluations from authoritative sources. Emphasis was placed on assays most frequently considered for hazard identification and risk assessment: mutation, clastogenicity and/or aneugenicity, and indirect DNA damage, such as changes in DNA repair mechanisms or gene expression data. These five sweeteners have been collectively evaluated in hundreds of in vivo or in vitro studies that employ numerous testing models, many of which have been conducted according to specific testing guidelines. The weight-of-evidence demonstrates overall negative findings across assay types for each sweetener when considering the totality of study design, reliability and reporting quality, as well as the lack of carcinogenic responses (or lack of responses relevant to humans) in animal cancer bioassays as well as observational studies in humans. This conclusion is consistent with the opinions of authoritative sources that have consistently determined that these sweeteners lack mutagenic and genotoxic potential.